Preliminary aspects toward the design and construction of efficient bio-mimics are in progress. A series of approximately (1) designed nicotinic acid "crown ethers" has been completed. The unexpected modes of complexation within or over the "crown ether" moiety has been evaluated by use of NMR shift reagent studies. Application of these studies to other multifunctional macrocycles will provide necessary insight into the location and preferences of metal ions in bio-models. The actual function of the carboxamide group in these models has been shown to be different for different modes of reduction. The connection atom (the one between the pyridine moiety and bridge) has been demonstrated to be the most important factor in the design of these bio-mimics. Currently, new synthetic routes to these nicotinic acid "crown ethers" from acyclic analogs is underway. Cyclizations of specific enamine intermediates generate the nicotinate ring directly in overall 50% yield. Complexation, reduction and subsequent hydride transfer studies are in progress. Application of several molecular constraints, found in our bio-models, has been shown to better explain the stereochemical aspects of cyclophanes. We have demonstrated that cyclophanes (or related macrocycles) possessing functionality that restricts the rotational freedom by an energetically preferred conformational orientation will have structural representations and isomerization processes considerably different from the classical approaches. From our studies, theoretical (Monte Carlo Calculations) and structural applications to simple polypeptides will afford us a better understanding of molecular geometries of biological systems. Introduction of pyrimidino subunits into a "crown ether" framework has generated a series of novel "uracil" macrocycle precursors. Thermolysis studies have demonstrated that the pyrimidino to uracil transformation is quite facile at 120-140 degrees C or at 30 degrees C, if Lewis acid catalyzed. During our studies attempting to improve the metal ion site selectivity in these biomodels, numerous 1:1-macrocyclic lactones were synthesized. In all cases, the yields were remarkably high and were a direct result of metal templation. Inclusion of potassium ion was favored with the homo 18-crown-6-analog. Numerous X-ray analyses of selected macrocycles were conducted.